Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21559 | 64900;64901;64902 | chr2:178584966;178584965;178584964 | chr2:179449693;179449692;179449691 |
| N2AB | 19918 | 59977;59978;59979 | chr2:178584966;178584965;178584964 | chr2:179449693;179449692;179449691 |
| N2A | 18991 | 57196;57197;57198 | chr2:178584966;178584965;178584964 | chr2:179449693;179449692;179449691 |
| N2B | 12494 | 37705;37706;37707 | chr2:178584966;178584965;178584964 | chr2:179449693;179449692;179449691 |
| Novex-1 | 12619 | 38080;38081;38082 | chr2:178584966;178584965;178584964 | chr2:179449693;179449692;179449691 |
| Novex-2 | 12686 | 38281;38282;38283 | chr2:178584966;178584965;178584964 | chr2:179449693;179449692;179449691 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/D | rs1191282845  |
-0.199 | 0.201 | N | 0.535 | 0.11 | 0.37281450598 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.97E-06 | 0 |
| A/D | rs1191282845 |
-0.199 | 0.201 | N | 0.535 | 0.11 | 0.37281450598 | gnomAD-4.0.0 | 4.10763E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49866E-06 | 0 | 1.65777E-05 |
| A/G | rs1191282845 |
None | 0.201 | N | 0.372 | 0.087 | 0.269111216191 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78011E-04 |
| A/G | rs1191282845 |
None | 0.201 | N | 0.372 | 0.087 | 0.269111216191 | gnomAD-4.0.0 | 3.10028E-06 | None | None | None | None | I | None | 1.33629E-05 | 3.33834E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.20441E-05 |
| A/T | rs1182073050 |
-0.549 | 0.201 | N | 0.382 | 0.111 | 0.260249123532 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| A/T | rs1182073050 |
-0.549 | 0.201 | N | 0.382 | 0.111 | 0.260249123532 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| A/T | rs1182073050 |
-0.549 | 0.201 | N | 0.382 | 0.111 | 0.260249123532 | gnomAD-4.0.0 | 6.5767E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47085E-05 | 0 | 0 |
| A/V | None | None | None | N | 0.043 | 0.084 | 0.229924730088 | gnomAD-4.0.0 | 2.05381E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.6992E-06 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.3786 | ambiguous | 0.3395 | benign | -0.869 | Destabilizing | 0.703 | D | 0.395 | neutral | None | None | None | None | I |
| A/D | 0.5925 | likely_pathogenic | 0.5746 | pathogenic | -0.403 | Destabilizing | 0.201 | N | 0.535 | neutral | N | 0.458942135 | None | None | I |
| A/E | 0.3673 | ambiguous | 0.3582 | ambiguous | -0.536 | Destabilizing | 0.143 | N | 0.467 | neutral | None | None | None | None | I |
| A/F | 0.3303 | likely_benign | 0.2912 | benign | -1.129 | Destabilizing | 0.538 | D | 0.561 | neutral | None | None | None | None | I |
| A/G | 0.2534 | likely_benign | 0.2268 | benign | -0.508 | Destabilizing | 0.201 | N | 0.372 | neutral | N | 0.488224892 | None | None | I |
| A/H | 0.4613 | ambiguous | 0.4451 | ambiguous | -0.527 | Destabilizing | 0.964 | D | 0.529 | neutral | None | None | None | None | I |
| A/I | 0.1182 | likely_benign | 0.1055 | benign | -0.496 | Destabilizing | None | N | 0.181 | neutral | None | None | None | None | I |
| A/K | 0.3308 | likely_benign | 0.3406 | ambiguous | -0.414 | Destabilizing | 0.001 | N | 0.27 | neutral | None | None | None | None | I |
| A/L | 0.134 | likely_benign | 0.1223 | benign | -0.496 | Destabilizing | 0.029 | N | 0.43 | neutral | None | None | None | None | I |
| A/M | 0.1538 | likely_benign | 0.1404 | benign | -0.404 | Destabilizing | 0.538 | D | 0.591 | neutral | None | None | None | None | I |
| A/N | 0.3156 | likely_benign | 0.2848 | benign | -0.2 | Destabilizing | 0.538 | D | 0.58 | neutral | None | None | None | None | I |
| A/P | 0.3182 | likely_benign | 0.3025 | benign | -0.451 | Destabilizing | 0.641 | D | 0.575 | neutral | N | 0.419764884 | None | None | I |
| A/Q | 0.3026 | likely_benign | 0.302 | benign | -0.508 | Destabilizing | 0.538 | D | 0.601 | neutral | None | None | None | None | I |
| A/R | 0.3131 | likely_benign | 0.3297 | benign | -0.051 | Destabilizing | 0.143 | N | 0.571 | neutral | None | None | None | None | I |
| A/S | 0.1113 | likely_benign | 0.104 | benign | -0.469 | Destabilizing | 0.094 | N | 0.432 | neutral | N | 0.444684758 | None | None | I |
| A/T | 0.0784 | likely_benign | 0.0731 | benign | -0.526 | Destabilizing | 0.201 | N | 0.382 | neutral | N | 0.41659408 | None | None | I |
| A/V | 0.0792 | likely_benign | 0.0762 | benign | -0.451 | Destabilizing | None | N | 0.043 | neutral | N | 0.378998484 | None | None | I |
| A/W | 0.8158 | likely_pathogenic | 0.8027 | pathogenic | -1.216 | Destabilizing | 0.964 | D | 0.587 | neutral | None | None | None | None | I |
| A/Y | 0.4834 | ambiguous | 0.4485 | ambiguous | -0.838 | Destabilizing | 0.703 | D | 0.599 | neutral | None | None | None | None | I |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.